[Interdisciplinary networks in diseases of peripheral nerves-Exemplified by the Tübingen nerve team]. / Interdisziplinäre Netzwerke bei Erkrankungen der peripheren Nerven ­ am Beispiel des Tübinger Nerve Teams.

BACKGROUND: Nerve damage can be autoimmune inflammatory, metabolic or traumatic, among others, and can be difficult to differentiate. OBJECTIVE: What are the advantages of interdisciplinary networks and how do they work? MATERIAL AND METHOD: Field report with case presentation from the University Hospital Tübingen in cooperation with the BG Accident Clinic Tübingen. CONCLUSION: Interdisciplinary networks improve the care of our patients and also serve as regular multidisciplinary continuing education.

[Public health situation of CIDP patients in nine German centers-neuritis network Germany]. / Versorgungssituation von CIDP-Patienten in neun deutschen Zentren des Neuritis Netzes.

BACKGROUND: Diagnosis and treatment of patients with immune-mediated neuropathies is challenging due to the heterogeneity of the diseases. OBJECTIVES: To assess similarities and differences in the current care of patients with immune-mediated polyneuropathies in specialized centers in Germany within the German neuritis network "Neuritis Netz". MATERIAL AND METHODS: We conducted a cross-sectional survey of nine neurological departments in Germany that specialize in the care of patients with immune-mediated neuropathies. We assessed the diagnosis, the approach to diagnostic work-up and follow-up, typical symptoms at manifestation and progression of the disease, and treatment data. RESULTS: This report includes data from 1529 patients per year treated for immune-mediated neuropathies, of whom 1320 suffered from chronic inflammatory demyelinating polyneuropathy (CIDP). Diagnostic work-up almost always included nerve conduction studies, electromyography, and lumbar puncture in accordance with current guidelines. The use of ultrasound, biopsy, and MRI varied. The most important clinical parameter for therapy monitoring in all centers was motor function in the clinical follow-up examinations. A wide range of different immunosuppressants was used for maintenance therapy in about 15% of patients. CONCLUSIONS: These data provide important epidemiological insights into the care of patients with immune-mediated neuropathies in Germany. The further development of specific recommendations for treatment and follow-up examinations is necessary to ensure a uniform standard of patient care. This effort is greatly facilitated by a structured collaboration between expert centers such as Neuritis Netz.

Nerve Ultrasound of Peripheral Nerves in Patients Treated with Immune Checkpoint Inhibitors.

Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60-77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1-2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0-2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8-13, p < 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.

[The interdisciplinary diagnostics and treatment of peripheral nerve lesions]. / Die interdisziplinäre Diagnostik und Versorgung peripherer Nervenverletzungen.

Nerve lesions are a frequent and often neglected problem in the daily routine of hospitals and clinical work and necessitate an intensive interdisciplinary treatment. In addition to correct anatomical allocation, the correct timing of the appropriate diagnostics, the timely decision for a possible intervention and the appropriate accompanying treatment are important prerequisites for a favorable prognosis. The basic diagnostics are, above all, neurography and electromyography after a sound clinical examination and documentation. In recent years both high-resolution ultrasound imaging and magnetic resonance imaging (MRI) of nerves have increasingly become established as indispensable diagnostic tools. In addition to describing the electrophysiological and sonographic principles, this article provides insights into surgical procedures, interdisciplinary cooperation and practical approaches.

Nerve Ultrasonography as an Additive Tool to Clinical Examination and Electrodiagnostics in Sporadic Mononeuritis - Imaging is the Key.

PURPOSE: Sporadic mononeuropathies without trauma or compression are challenging to diagnose. Nerve ultrasound has recently proven its usefulness in the diagnosis of traumatic neuropathies, tumors and polyneuropathies. However, its role in mononeuropathies currently remains unclear. We describe ultrasonography follow-up results in 12 patients with suggested spontaneous, monophasic mononeuritis without signs of generalization. MATERIALS AND METHODS: Nerve conduction studies (NCS), ultrasonography of the affected nerves and the contralateral side, laboratory analysis, and if possible magnetic resonance imaging (MRI) of the affected nerves were established in all patients at onset. In one patient, additive nerve biopsy was performed. In all patients, ultrasonography was repeated after immunotherapy. RESULTS: An infectious pathogen of neuritis was not found in any patient. All but one patient showed predominant axonal nerve damage in NCS, whereas ultrasonography and MRI revealed fascicular and/or overall cross-sectional area (CSA) enlargement or T2 hyperintensity of the affected nerve segments, suggesting an inflammatory background of the neuropathy. Most patients showed significant clinical amelioration of symptoms under treatment (75.0 %) and consequently a decrease in CSA/fascicle enlargement over time (77.8 %). CONCLUSION: Ultrasonography and MRI of the nerves revealed enlargement in patients with mononeuropathy of axonal NCS pattern of unknown origin. Ultrasonography can facilitate the therapeutic decision for immunotherapy. Next to nerve trauma, nerve tumors and nerve entrapments, ultrasonography reliably shows nerve enlargement in the case of inflammation and therefore could further enrich neurophysiology. Nerve imaging might serve as a follow-up tool by observing a decrease in nerve enlargement and improved function.

Neuropathy in ARSACS is demyelinating but without typical nerve enlargement in nerve ultrasound.

BACKGROUND: To specify peripheral nerve affection in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) by correlating high-resolution nerve ultrasound and nerve conduction studies. METHODS: We assessed a cohort of 11 ARSACS patients with standardized nerve conduction studies and high-resolution ultrasound of peripheral nerves and compared nerve ultrasound findings to a healthy control group matched for age, sex, size and weight. RESULTS: Mean age of patients was 39.0 (± 14.1) years and disease duration at assessment 30.6 (± 12.5) years. All patients presented with a spasticity, ataxia and peripheral neuropathy. Neuropathy appeared to be primarily demyelinating in 9/11 cases and was not classifiable in 2/11 cases due to not evocable potentials. Nerve ultrasound revealed a normal ultrasound pattern sum score (UPSS) in each ARSACS patient and no significant nerve enlargement compared to the control group. CONCLUSIONS: Peripheral neuropathy in ARSACS showed primarily demyelinating rather than axonal characteristics and presented without nerve enlargement. As demyelinating neuropathies do commonly present enlarged nerves we recommend further genetic testing of the SACS gene in patients who present with this combination of demyelinating neuropathy without nerve enlargement. ARSACS cases that initially presented only with neuropathy without spasticity or ataxia and therefore were misdiagnosed as Charcot-Marie-Tooth disease are supporting this suggestion.

Multihit Injury of the Radial Nerve in a 62-year-old Woman: A Case Report.

We report the case of a 62-year-old female patient with a triple-crush radial nerve injury, diagnosed in subsequent order following a fracture of the left humerus. The patient developed flaccid paralysis of all muscles innervated by the left radial nerve except the triceps brachii and reported a sensory deficit corresponding to the innervation territories of the posterior nerve of the forearm as well as the superficial branch of the radial nerve. Following neurolysis of the radial nerve at the humerus level, wrist extension as well as sensory perception on the dorsal aspect of the forearm recovered, but finger extension and thumb abduction were still impossible. Following neurological evaluation and nerve ultrasound, supinator syndrome was diagnosed and the patient underwent decompression surgery. Following surgical decompression, motor recovery was observable but a sensory deficit remained in the area innervated by the superficial branch of the radial nerve. In consequence, the third crush injury of the left radial nerve, that is, Wartenberg syndrome or cheiralgia paraesthetica was diagnosed. Decompression surgery of the superficial branch of the radial nerve was performed and the patient reported profound amelioration of her sensory symptoms during a follow-up examination at our outpatient clinic 6 weeks postoperatively.

Muscle Ultrasound Shear Wave Elastography as a Non-Invasive Biomarker in Myotonia.

Myotonia, i.e., delayed muscle relaxation in certain hereditary muscle disorders, can be assessed quantitatively using different techniques ranging from force measurements to electrodiagnostics. Ultrasound shear wave elastography (SWE) has been proposed as a novel tool in biomechanics and neuromuscular medicine for the non-invasive estimation of muscle elasticity and, indirectly, muscle force. The aim of this study is to provide 'proof-of-principle' that SWE allows a quantitative measurement of the duration of delayed muscle relaxation in myotonia in a simple clinical setting. In six myotonic muscle disorder patients and six healthy volunteers, shear wave velocities (SWV) parallel to the fiber orientation in the flexor digitorum superficialis muscle in the forearm were recorded with a temporal resolution of one per second during fist-clenching and subsequent relaxation; the relaxation time to 10% of normalized shear wave velocity (RT0.1) was calculated. Forty-six SWE imaging sequences were acquired, yielding a mean RT0.1 of 7.38 s in myotonic muscle disorder patients, significantly higher than in healthy volunteers (1.36 s), which is comparable to data obtained by mechanical dynamometry. SWV measurements during the baseline relaxation and voluntary contraction phases did not differ significantly between groups. We conclude that SWE is a promising, non-invasive, widely available tool for the quantitative assessment of myotonia to aid in diagnosis and therapeutic monitoring.

Nerve Ultrasound as Helpful Tool in Polyneuropathies.

BACKGROUND: Polyneuropathies (PNP) are a broad field of diseases affecting millions of people. While the symptoms presented are mostly similar, underlying causes are abundant. Thus, early identification of treatable causes is often difficult. Besides clinical data and basic laboratory findings, nerve conduction studies are crucial for etiological classification, yet limited. Besides Magnetic Resonance Imaging (MRI), high-resolution nerve ultrasound (HRUS) has become a noninvasive, fast, economic and available tool to help distinguish different types of nerve alterations in neuropathies. METHODS: We aim to describe typical ultrasound findings in PNP and patterns of morphological changes in hereditary, immune-mediated, diabetic, metabolic and neurodegenerative PNP. Literature research was performed in PubMed using the terms 'nerve ultrasound', neuromuscular ultrasound, high-resolution nerve ultrasound, peripheral nerves, nerve enlargement, demyelinating, hereditary, polyneuropathies, hypertrophy'. RESULTS: Plenty of studies over the past 20 years investigated the value of nerve ultrasound in different neuropathies. Next to nerve enlargement, patterns of nerve enlargement, echointensity, vascularization and elastography have been evaluated for diagnostic terms. Furthermore, different scores have been developed to distinguish different etiologies of PNP. CONCLUSIONS: Where morphological alterations of the nerves reflect underlying pathologies, early nerve ultrasound might enable a timely start of available treatment and also facilitate follow up of therapy success.

High-Resolution Nerve Ultrasound Abnormalities in POEMS Syndrome-A Comparative Study.

BACKGROUND: High-resolution nerve ultrasound (HRUS) has been proven to be a valuable tool in the diagnosis of immune-mediated neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is an important differential diagnosis of CIDP. Until now, there have been no studies that could identify specific HRUS abnormalities in POEMS syndrome patients. Thus, the aim of this study was to assess possible changes and compare findings with CIDP patients. METHODS: We retrospectively analyzed HRUS findings in three POEMS syndrome and ten CIDP patients by evaluating cross-sectional nerve area (CSA), echogenicity and additionally calculating ultrasound pattern scores (UPSA, UPSB, UPSC and UPSS) and homogeneity scores (HS). RESULTS: CIDP patients showed greater CSA enlargement and higher UPSS (median 14 vs. 11), UPSA (median 11.5 vs. 8) and HS (median 5 vs. 3) compared with POEMS syndrome patients. However, every POEMS syndrome patient illustrated enlarged nerves exceeding reference values, which were not restricted to entrapment sites. In CIDP and POEMS syndrome, heterogeneous enlargement patterns could be identified, such as inhomogeneous, homogeneous and regional nerve enlargement. HRUS in CIDP patients visualized both increased and decreased echointensity, while POEMS syndrome patients pictured hypoechoic nerves with hyperechoic intraneural connective tissue. Discussion: This is the first study to demonstrate HRUS abnormalities in POEMS syndrome outside of common entrapment sites. Although nerve enlargement was more prominent in CIDP, POEMS syndrome patients revealed distinct echogenicity patterns, which might aid in its differentiation from CIDP. Future studies should consider HRUS and its possible role in determining diagnosis, prognosis and treatment response in POEMS syndrome.

Peripheral Nerve Imaging Aids in the Diagnosis of Immune-Mediated Neuropathies-A Case Series.

BACKGROUND: Diagnosis of immune-mediated neuropathies and their differentiation from amyotrophic lateral sclerosis (ALS) can be challenging, especially at early disease stages. Accurate diagnosis is, however, important due to the different prognosis and available treatment options. We present one patient with a left-sided dorsal flexor paresis and initial suspicion of ALS and another with multifocal sensory deficits. In both, peripheral nerve imaging was the key for diagnosis. METHODS: We performed high-resolution nerve ultrasound (HRUS) and 7T or 3T magnetic resonance neurography (MRN). RESULTS: In both patients, HRUS revealed mild to severe, segmental or inhomogeneous, nerve enlargement at multiple sites, as well as an area increase of isolated fascicles. MRN depicted T2 hyperintense nerves with additional contrast-enhancement. DISCUSSION: Peripheral nerve imaging was compatible with the respective diagnosis of an immune-mediated neuropathy, i.e., multifocal motor neuropathy (MMN) in patient 1 and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) in patient 2. Peripheral nerve imaging, especially HRUS, should play an important role in the diagnostic work-up for immune-mediated neuropathies and their differentiation from ALS.

Normative Observational Nerve Ultrasound Values in School-Age Children and Adolescents and Their Application to Hereditary Neuropathies.

Backgrounds: We have aimed to establish nerve ultrasound reference data in 8 to 17-year-old children and adolescents and to compare those data to younger children, adults, and age-matched children with polyneuropathies. Methods: High-resolution ultrasounds of the nerves were performed in 117 healthy children and adolescents at 20 predefined landmarks in the neck and the extremities of both sides. Mean values, side-to-side differences and intraneural ratios, as well as upper limits have been calculated. In a second step, a comparison between 25 children and adolescents of the same age range with proven hereditary and acquired neuropathies and lysosomal storage diseases has been carried out. Results: Nerve growth correlates significantly with age and reaches adult values at the age of around 15 years. The influence of body mass index and gender is negligible at most segments. By the use of age-specific upper limits, nerve enlargement could be seen in distinct types of neuropathies, particularly in demyelinating hereditary and inflammatory types, which is comparable to findings in adults, but also in rare lysosomal storage diseases. Conclusion: Nerve size correlates with age during childhood and reaches a climax in younger adults. Age-matched reference data are inevitable to differ between hypertrophic and non-hypertrophic nerve damage, e.g., in neuropathies.

Nerve ultrasound reference data in children from two to seven years.

OBJECTIVE: We examined selected peripheral and spinal nerves of children aged between two and seven years. METHOD: High resolution ultrasound was performed in 116 children (2-7 years of age) at 19 predefined landmarks of median, ulnar, tibial, fibular, sural and radial nerves, the vagus as well as cervical spinal nerve 5 and 6. Further, side-to-side measuring and grey-scale analysis was done at selected nerve sites. RESULTS: Nerves of children were on average smaller than those of adults. Nerve growth correlates significantly with age in all nerves, the mean values were similar in the age of two to four years and five to seven years. Body mass index (BMI) and gender showed moderate effect at some nerve sites, however not uniformly in all. A side-to-side difference of up to 30% in median, and up to 20% in tibial nerve can occur in healthy individuals. Grey-scale analysis for echointensity has been performed in median, ulnar and tibial nerves. CONCLUSION: Nerve size increases with age, BMI and gender have moderate effect. A side-to-side-difference of up to 30% can exist. SIGNIFICANCE: Reference values of nerve cross-sectional area, side-to-side-difference and echo intensity are necessary to detect nerve pathology in children as well as in adults.